Vascular Caliber Research Articles

Associations between dietary flavonoids and retinal microvasculature in older adults.

In this study, we assessed whether there are independent associations between dietary total flavonoid intake and major flavonoid classes with retinal arteriolar and venular calibre. Blue Mountains Eye Study participants aged 49+ years who had complete data on diet and retinal vessel measures were analysed (n = 2821). Dietary intake was assessed using a semi-quantitative Food-Frequency Questionnaire (FFQ). Flavonoid content of foods in the FFQ was estimated using the US Department of Agriculture Flavonoid, Isoflavone and Proanthocyanidin databases. Fundus photographs were taken and retinal vascular calibre was measured using validated computer-assisted techniques. The associations of intake of dietary flavonoids with retinal vessel calibre were examined in linear regression models and general linear model. The highest quartile of intake was compared with the lowest quartile using multivariable-adjustment models. Participants with the highest proanthocyanidin intake had narrower retinal venules (223.9 ± 0.62 versus 226.5 ± 0.63, respectively; Ptrend = 0.01); and the highest isoflavone intake was associated with wider retinal arterioles (188.1 ± 0.55 versus 186.3 ± 0.56, respectively; Ptrend = 0.01). The highest apple/pear consumption (a dietary source of catechin) was associated with narrower retinal venules (223.8 ± 0.57 versus 226.1 ± 0.52; Ptrend = 0.01) and wider retinal arterioles (187.9 ± 0.51 versus 186.2 ± 0.51; Ptrend = 0.02). Further, participants who were in the highest versus lowest quartile of chocolate consumption had ~ 2.1μm narrower retinal venules (multivariable-adjusted P = 0.03). This study shows that higher intakes of specific flavonoid subclasses are associated with a favourable retinal microvascular profile. Greater consumption of flavonoid-rich apples/pears and chocolate was also associated with beneficial variations in retinal vascular calibre.

Abstract P135: Angiotensin II, But Not Methoxamine Or 5-HT, Causes ATP Release in the Rat Mesenteric Arterial Bed

The control of vascular caliber relies on mediators released from multiple components of the vascular neuroeffector junction. These mediators include ATP, which is released from the sympathetic nerves from vesicles that also contain norepinephrine, as well as from the vascular smooth muscle (VSM) via pannexin-1 (panx-1) channels. We hypothesize that VSM-derived ATP plays a critical role in balancing the vasoactive effects of mediators at the vascular neuroeffector junction. Panx-1 channel opening on VSM has been reported to be stimulated by caspase cleavage, cytoplasmic Ca 2+ , and extracellular K + , but the effects of VSM GPCR activation are not as well characterized. Here we utilize a near-real time luminometric technique to quantify the release of ATP from the rat mesenteric arterial bed in response to vasoconstrictor agonists. We observed disparate effects of three physiologically relevant vasoactive agents, and these do not correlate with the relative changes in perfusion pressure. Whereas angiotensin II caused a robust release of ATP (228.6 ± 31.94 nM), no significant release was observed with either methoxamine (an α 1 agonist; 44.41 ± 31.94 nM) or 5-HT (0 ± 0 nM) . These results indicate that GPCR-mediated smooth muscle contraction is not sufficient to induce ATP release in this vascular bed. This is an important first step toward understanding the role of ATP in the vasculature.

Retinal vascular tortuosity in schizophrenia and bipolar disorder

The micro-vasculature of retina and brain share common morphological, physiological, and pathological properties. Retina being easily accessible, retinal vascular examination provides an indirect assessment of cerebral vasculature. Considering the high prevalence of vascular morbidity in SCZ and BD a few studies have examined retinal vascular caliber and have reported increased retinal venular caliber in schizophrenia (SCZ). Retinal vascular tortuosity could serve as a better structural measure than caliber as it is static and less susceptible to pulse period variations. However, to date, no study has examined retinal vascular tortuosity in SCZ and bipolar disorder (BD). Hence, we examined retinal vascular tortuosity in comparison with healthy volunteers (HV). We included 255 subjects (78 HV, 79 SCZ, and 86 BD) in the age range of 18 to 50 years. Trained personnel acquired images using a non-mydriatic fundus camera. To measure the average retinal arteriolar tortuosity index (RATI) and retinal venular tortuosity index (RVTI), we used a previously validated, semi-automatic algorithm. The results showed significant differences across the three groups in RATI but not in RVTI; both BD and SCZ had significantly increased RATI compared to HV. There was also a significant difference between SCZ and BD, with BD having higher RATI. If shown to be of predictive utility in future longitudinal studies, it has the potential to identify patients at risk of development of adverse vascular events. As retinal vascular imaging is non-invasive and inexpensive, it could serve as a proxy marker and window to cerebral vasculature.

Association of dietary nitrate intake with retinal microvascular structure in older adults.

Existing research suggests that changes to retinal vascular caliber reflect nitric oxide (NO)-dependent endothelial dysfunction. Dietary nitrate is an important source of NO; however, studies on the link between dietary nitrate intake and retinal microvasculature are lacking. We aimed to assess the cross-sectional association between intake of dietary nitrate (from vegetable and non-vegetable sources) and retinal arteriolar and venular caliber among older adults. Participants from the Blue Mountains Eye Study aged 49+ years with complete data at baseline on diet and retinal vessel measures were analyzed (n = 2813). Dietary intake was assessed using a validated semi-quantitative food-frequency questionnaire. Nitrate intake from vegetable and non-vegetable sources was estimated using a validated comprehensive database and other published data where necessary. Fundus photographs were taken and retinal vascular caliber measured using validated computer-assisted techniques and summarized. Participants in the lowest versus highest tertile of vegetable nitrate intake had significantly narrower retinal arterioles: 186.2 ± 0.48 versus 187.6 ± 0.48µm (multivariable-adjusted p = 0.04). After multivariable adjustment, each 10-unit higher intake of total nitrate and vegetable nitrate was associated with 0.089 ± 0.004 and 0.090 ± 0.004µm wider retinal arteriolar caliber, respectively, both p = 0.03. Each 10-unit higher vegetable nitrate intake was associated with 0.092 ± 0.005µm narrower retinal venules (p = 0.05). Intake of dietary nitrate, particularly from vegetable sources, was associated with beneficial variations in both retinal arteriolar and venular caliber among older adults. Further research into associations between dietary nitrate and the retinal microvasculature could allow for greater understanding and possible prevention of clinical cardiovascular events.

Heart rate variability, the dynamic nature of the retinal microvasculature and cardiac stress: providing insight into the brain-retina-heart link: the SABPA study.

Decreased heart-rate-variability (HRV) indicates increased sympathetic nervous system (SNS) activity and modulation with a shift in the sympatho-vagal balance towards SNS predominance. Increased SNS activity may precede volume-loading hypertension, contribute to increases in cardiac troponin T (cTnT), endothelial dysfunction and small vessel disease. Therefore, we investigated the retinal vasculature, HRV during flicker-light-induced-provocation (FLIP) and systemic cTnT, a marker of cardiac stress, to provide further evidence in support of the brain-retina-heart link. Cross-sectional observations were obtained from a bi-ethnic cohort (N = 264), aged 23-68 years. Fasting serum samples for cTnT were obtained. Retinal vascular calibres were quantified from mydriatic eye fundus images and dynamic retinal vessel calibre responses were determined during FLIP. Time-and frequency domain parameters of HRV were calculated during FLIP for each participant. Africans had wider venules and attenuated time domain parameters during FLIP. In Africans, inverse associations emerged between arteriolar dilation and both cTnT and root-mean squared of the standard deviations of successive RR-intervals (rMSSD) (p = 0.030), and between arteriolar constriction and both low-frequency expressed in normalised units (LFnu) (p = 0.003) and high-frequency expressed in normalised units (p = 0.021). Wider venules inversely associated with standard deviation of the NN intervals (SDNN) as well as LFnu (p = 0.009) in Africans. An opposite profile was observed in Caucasians with both time-and frequency domain parameters of HRV in relation to retinal vessel structure and function. FLIP elicited increased SNS activity and modulation in this bi-ethnic cohort. In Africans, decreased HRV during FLIP accompanied arteriolar and venular responses and elevated systemic levels of cTnT, implying that the SNS exerted a significant effect on the smooth muscle tone of the retinal vasculature. Disrupted retinal autoregulation may imply general autonomic nervous system dysfunction; exemplifying central control by the brain on all systemic regulatory functions, across different vascular beds.

Effect of Pupil Dilation with Tropicamide on Retinal Vascular Caliber

ABSTRACTPurpose: The retinal blood vessels reflect changes in the brain’s micro-circulation and these changes have been shown to correlate with the incidence of diseases such as stroke, heart disease and Alzheimer’s disease. Studies investigating the retinal vasculature routinely use pupil dilation with tropicamide to optimize image acquisition and quality. The aim of this study was to investigate the effects of tropicamide on retinal vascular parameters using retinal photography.Methods: The study was performed on 41 healthy young subjects of both sexes, using tropicamide to dilate only the right pupil, leaving the left as a control.Results: Pupil dilation with tropicamide resulted in reduced retinal vessel width measures based on standardized approaches, particularly reduced arteriolar caliber (p < .0005). However, closer investigation of the images revealed reduced fundus image magnification in the post-tropicamide images, based on reduced optic nerve head diameter (p < .0005) and longitudinal analysis with image registration and affine transformation (p < .0001). No change in vessel width parameters was observed after adjustment for image magnification.Conclusion: These results suggest that tropicamide does not change the width of the retinal vessels, however width parameters as measured by standard approaches may be reduced due to image magnification changes resulting from cycloplegia. In this study, improved optic nerve head segmentation for image scale conversion removed the magnification error. With this correction, the tropicamide intervention had no effect on vessel width parameters in young healthy people and could be utilized in future without affecting the results of retinal vascular analysis.

THE THICKNESSES OF CHOROID, MACULAR SEGMENTS, PERIPAPILLARY RETINAL NERVE FIBER LAYER, AND RETINAL VASCULAR CALIBER IN HIV-1-INFECTED PATIENTS WITHOUT INFECTIOUS RETINITIS.

To evaluate choroidal, macular, peripapillary retinal nerve fiber layer (RNFL) thicknesses and retinal vascular caliber alterations in HIV-1-infected patients without opportunistic infections. This cross-sectional study included 45 HIV-1-infected patients and 47 healthy subjects. Spectral domain optical coherence tomography was used for assessment of choroidal, macular, peripapillary RNFL thicknesses and retinal vascular caliber alterations. The mean CD4 count was 426 ± 226 cells per milliliter and the mean HIV-1 RNA level was 1.8 × 10 ± 3.6 × 10 copies/mL in HIV-infected group. Central inner plexiform, superior photoreceptor, superior and nasal retinal pigment epithelium layers were thinner in HIV-infected patients compared with control subjects (P < 0.05). The differences in sectoral retinal thicknesses lost their significance after Bonferroni correction (P < 0.01). The average thickness of pericentral retina within 3 mm was thinner in the photoreceptor layer in HIV-infected patients compared with control subjects (P = 0.033). The differences in peripapillary RNFL thickness, choroidal thickness, and retinal vascular caliber were not significant between the groups. Choroidal thickness and pericentral outer plexiform were thinner, whereas peripapillary RNFL was thicker in newly diagnosed cases (16 patients) compared with patients having treatment for at least 4 months or longer (27 patients, P < 0.05, Mann-Whitney U test). HIV-1 RNA showed negative correlation with choroidal thickness (r = -0.435, P = 0.003) and positive correlation with peripapillary RNFL in central (r = 0.323, P = 0.032) and superonasal (r = 0.369, P = 0.014) sectors. Choroidal thickness was thinner in newly diagnosed patients compared with patients on treatment. Viral load showed negative correlation with choroidal thickness. Retinal segmental alterations occurred in HIV-infected patients compared with control subjects.

Retinal microvasculature: population epidemiology and concordance in Australian children aged 11-12 years and their parents.

ObjectivesTo describe distributions and concordance of retinal microvasculature measurements in a population-based sample of Australian parent–child dyads at child age 11–12 years.DesignCross-sectional Child Health CheckPoint study, between waves 6 and 7 of the national population-based Longitudinal Study of Australian Children (LSAC).SettingAssessment centres in seven Australian cities, February 2015–March 2016.ParticipantsOf the 1874 participating families, 1288 children (51% girls) and 1264 parents (87% mothers, mean age 43.7) were analysed. Diabetic participants and non-biological pairs were excluded from concordance analyses.Outcome measuresRetinal photographs were taken by non-mydriatic fundus camera. Trained graders scored vascular calibre using semi-automated software, yielding estimates of central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) and arteriolar–venular ratio (AVR). Pearson’s correlation coefficients and multivariable linear regression models assessed parent–child concordance. Survey weights and methods accounted for LSAC’s complex sampling, stratification and clustering within postcodes.ResultsMean (SD) of CRAE and CRVE were larger in children (159.5 (11.8) and 231.1 (16.5) μm, respectively) than parents (151.5 (14.0) and 220.6 (19.0) μm), yielding similar AVR (children 0.69 (0.05), parents 0.69 (0.06)). Correlation coefficients for parent–child pairs were 0.22 (95% CI 0.16 to 0.27) for CRAE, 0.23 (95% CI 0.17 to 0.28) for CRVE and 0.18 (95% CI 0.13 to 0.24) for AVR. Mother–child and father–child values were similar (0.20 and 0.32 for CRAE, 0.22 and 0.29 for CRVE, respectively). Relationships attenuated slightly on adjustment for age, sex, blood pressure, diabetes and body mass index. Percentiles and concordance are presented for the whole sample and by sex.ConclusionsArteriolar and venular calibre were similar to previously documented measures in midlife adult and late childhood populations. Population parent–child concordance values align with moderate polygenic heritability reported in smaller studies.

In-vivo MRI Reveals Changes to Intracerebral Vasculature Caliber in HIV Infection.

Objective: To characterize cerebral arterial remodeling in HIV-infected (HIV+) individuals in-vivo, and to study its clinical and immunological associations.Methods: T2*-weighted magnetic resonance imagining sequences was used to determine cross-sectional area (vascular caliber) of the anterior (A1 segment) and middle (M1 segment) cerebral arteries in HIV- (control) and HIV+ subjects on antiretroviral therapy. Correlations of A1 caliber with clinical, demographic parameters, and immunological markers in cerebrospinal fluid (CSF) were determined using multivariable analyses.Results: A1 and M1 calibers from 22 HIV- control subjects (age: median 48.5 years, range 22-60 years, 55% male) and 61 HIV+ subjects (age: median 53 years, range 25–60 years, 67% male) were studied. ANCOVA, adjusting for ethnicity and sex (age was not correlated with M1 or A1 caliber in either group), revealed that HIV+ subjects had larger caliber in the A1 segment than HIV- subjects (4.95 ± 0.14 mm2, and 4.47 ± 0.21 mm2 respectively, p = 0.048), but caliber of the M1 segment did not differ among the groups (7.21 ± 0.14 mm2 and 7.09 ± 0.23 mm2 respectively, p = 0.65). In the HIV+ cohort, longer disease duration and higher current CD4 T-cell count were associated with reduced A1 caliber (r =−0.42 and −0.33 respectively, p < 0.05). In addition, increase in cardiovascular disease risk (CVD risk) was associated with a decrease in A1 caliber in the HIV group (r = −0.35, p < 0.05).Conclusions: This cross-sectional study reveals an increase in A1 caliber in the HIV+ cohort, compared to control subjects, which is especially prominent in early phase of the disease. This increase in caliber may be associated with acute pathological processes in HIV during the initial stages of infection resulting in loss of compliance or thinning of the arterial wall. At later stages, such changes may be confounded by arteriosclerotic changes that are common in later stages of HIV infection. This study suggests there is extensive vessel remodeling in various stages of infection. Long-term longitudinal follow-up of this cohort is planned to further verify this hypothesis and to better understand this MRI marker of intracranial vascular caliber.

Supervised Machine Learning Based Multi-Task Artificial Intelligence Classification of Retinopathies

Artificial intelligence (AI) classification holds promise as a novel and affordable screening tool for clinical management of ocular diseases. Rural and underserved areas, which suffer from lack of access to experienced ophthalmologists may particularly benefit from this technology. Quantitative optical coherence tomography angiography (OCTA) imaging provides excellent capability to identify subtle vascular distortions, which are useful for classifying retinovascular diseases. However, application of AI for differentiation and classification of multiple eye diseases is not yet established. In this study, we demonstrate supervised machine learning based multi-task OCTA classification. We sought (1) to differentiate normal from diseased ocular conditions, (2) to differentiate different ocular disease conditions from each other, and (3) to stage the severity of each ocular condition. Quantitative OCTA features, including blood vessel tortuosity (BVT), blood vascular caliber (BVC), vessel perimeter index (VPI), blood vessel density (BVD), foveal avascular zone (FAZ) area (FAZ-A), and FAZ contour irregularity (FAZ-CI) were fully automatically extracted from the OCTA images. A stepwise backward elimination approach was employed to identify sensitive OCTA features and optimal-feature-combinations for the multi-task classification. For proof-of-concept demonstration, diabetic retinopathy (DR) and sickle cell retinopathy (SCR) were used to validate the supervised machine leaning classifier. The presented AI classification methodology is applicable and can be readily extended to other ocular diseases, holding promise to enable a mass-screening platform for clinical deployment and telemedicine.

Association between radiation, glaucoma subtype, and retinal vessel diameter in atomic bomb survivors

We examined the relationship between glaucoma subtype and retinal vascular caliber as markers of ocular circulation. Subjects were Japanese atomic bomb survivors in Hiroshima and Nagasaki. After a screening examination, potential cases were subjected to further definitive examination. The diameters of central retinal artery and vein equivalents (CRAE and CRVE) on digitized retinal photographs were measured using an established method. Generalized linear regression analyses were used to examine the associations among vessel diameters, radiation exposure, and prevalence of glaucoma subtypes among the study subjects. We identified 196 cases of glaucoma (12%) based on optic disc appearance, perimetry results, and other ocular findings. The main subtypes were primary angle-closure glaucoma, primary open-angle glaucoma and normal-tension glaucoma (NTG). NTG was the dominant subtype (78%). NTG was negatively associated with CRAE and CRVE, and positively associated with radiation dose. CRVE was negatively associated with radiation dose and the association was unclear for CRAE. The smaller retinal vessel caliber in NTG patients than in subjects without glaucoma may indicate an association between ocular blood flow and the pathogenesis of NTG. However, significant relationships among vessel calibers, NTG and radiation exposure were not clear.

The Comparison of Morphologic Characteristics of Type 1 and Type 2 Choroidal Neovascularization in Eyes with Neovascular Age-Related Macular Degeneration using Optical Coherence Tomography Angiography

Purpose: The purpose of this study was to use optical coherence tomography angiography (OCTA) to compare the morphology characteristics of type 1 and 2 choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD) patients. Materials and Methods: This is a retrospective, observational study of 51 eyes with nAMD using OCTA from July 2016 through March 2017. Results: In total, 51 eyes of 50 patients were included in the analysis. According to the anatomical classification based on OCT, 27 eyes (53%) were diagnosed with type 1 CNV, and 24 eyes (47%) were type 2 CNV. Type 2 CNV was characterized by smaller flow area, smaller greatest vascular caliber (GVC), smaller greatest linear dimension (GLD), and shorter duration of disease. The duration of disease only correlated with GVC (p = 0.026) in multivariate linear regression results. Meanwhile, GLD correlated with GVC and flow area whereas GVC was not associated with flow area. Conclusion: This study demonstrated that type 2 CNV was characterized by shorter duration of disease, smaller GVC, smaller GLD, and smaller flow area compared with type 1 CNV. Additionally, we showed that the duration of the disease correlated with GVC of the CNV.

Association of Systemic Inflammation With Retinal Vascular Caliber in Patients With AIDS.

PurposeTo evaluate relationships among retinal vascular caliber and biomarkers of systemic inflammation in patients with AIDS.MethodsA total of 454 participants with AIDS had retinal vascular caliber (central retinal artery equivalent and central retinal vein equivalent) determined from enrollment retinal photographs by reading center graders masked to clinical and biomarker information. Cryopreserved plasma specimens were assayed for inflammatory biomarkers, including C-reactive protein (CRP), IL-6, interferon-γ inducible protein (IP)-10, kynurenine/tryptophan (KT) ratio, and intestinal fatty acid binding protein (I-FABP).ResultsIn the simple linear regression of retinal vascular caliber on plasma biomarkers, elevated CRP, IL-6, and IP-10 were associated with retinal venular dilation, and elevated KT ratio with retinal arteriolar narrowing. In the multiple linear regression, including baseline characteristics and plasma biomarkers, AMD was associated with dilation of retinal arterioles (mean difference: 9.1 μm; 95% confidence interval [CI] 5.2, 12.9; P < 0.001) and venules (mean difference, 10.9 μm; 95% CI, 5.3, 16.6; P < 0.001), as was black race (P < 0.001). Hyperlipidemia was associated with retinal venular narrowing (mean difference, −7.5 μm; 95% CI, −13.7, −1.2; P = 0.02); cardiovascular disease with arteriolar narrowing (mean difference, −5.2 μm; 95% CI, −10.3, −0.1; P = 0.05); age with arteriolar narrowing (slope, −0.26 μm/year; 95% CI, −0.46, −0.06; P = 0.009); and IL-6 with venular dilation (slope, 5.3 μm/standard deviation log10[plasma IL-6 concentration]; 95% CI, 2.7, 8.0; P < 0.001).ConclusionsThese data suggest that retinal vascular caliber is associated with age, race, AMD, hyperlipidemia, cardiovascular disease, and selected biomarkers of systemic inflammation.

Abnormal retinal microvasculature found in active rheumatoid arthritis:a different perspective of microvascular health

Background/aim We aimed to assess the association between retinal vascular caliber (RVC) scores and disease activity in rheumatoid arthritis (RA) patients.Materials and methods Forty-seven RA patients, 32 systemic lupus erythematosus (SLE) patients, and 45 healthy people were enrolled. RA and SLE patients were subdivided into groups according to C-reactive protein (CRP) levels. RA patients were also grouped according to Disease Activity Score-28 (DAS-28). Fundus photography was performed for all patients. RVC was summarized as the central retinal artery and vein equivalents (CRAE and CRVE).Results Mean CRVE for RA patients was 213.3 ± 17.8 µm compared with 209.2 ± 14.1 µm for SLE and 217.5 ± 26.2 µm for the control group (P = 0.17). RVC scores did not differ between the CRP-high and CRP-low groups. As the RA disease activity increased, the widening of CRVE became more prominent and statistically significant. When the DAS-28 > 5.1 (CRVE, 220.4 (211.8–246.5) µm) group and DAS-28 ≤ 3.2 (CRVE, 214.4 (172.4–242.3) µm) group were compared, statistical significance was more pronounced (P = 0.03) than when comparing the DAS-28 > 3.2 and DAS-28 ≤ 3.2 groups (P = 0.05). Conclusion CRVE, which reflects systemic inflammation and possibly increased cardiovascular risk, was significantly increased in active RA patients. The association between retinal venular widening and disease activity, regardless of CRP, may be a sign that RA-related inflammation may have systemic vascular effects even with normal levels of CRP.

Cerebrovascular pathology in cerebral amyloid angiopathy presenting as intracerebral haemorrhage.

Cerebral amyloid angiopathy (CAA) is the second most common cause of non-traumatic intracerebral haemorrhage (ICH) accounting for 12-15% of lobar haemorrhages inthe elderly. Definitive diagnosis of CAA requires histological evaluation. We aimed to evaluate the spectrum of cerebrovascular changes in CAA-related ICH. Between 2011 and 2015, biopsy-confirmed cases of CAA were retrieved and clinical, radiological and pathological featureswere reviewed. The spectrum of vascular alterations was evaluated and amyloid deposition was graded in accordance with the Greenberg and Vonsattel scale. Seven cases of sporadic CAA [5 males and 2 females] were diagnosed, none of whom were suspected to have CAA pre-operatively. Six presented with large intracerebral haematoma (ICH) requiring neurosurgical intervention (age range: 56-70years) and one had episodic headache and multiple microhaemorrhages requiring a diagnostic brain biopsy (45years). In the presence of large ICH, vascular amyloid deposits were of moderate to severe grade (grade 4 in 4, grades 2 and 3 in 1 case each) with predominant involvement of medium (200-500μm) to large (> 500μm) leptomeningeal vessels. Fibrinoid necrosis was noted in four. Two were hypertensive and on antiplatelet agents. β-Amyloid plaques were detected in two, one of whom had symptomatic dementia. MRI performed in 3 of 6 cases with ICH did not reveal any microhaemorrhages. Amyloid deposits in small (50-200μm) to medium (200-500μm) calibre intracortical vessels produced parenchymal microhemorrhages. Histopathological examination of ICH is essential for diagnosing CAA. The vascular calibre rather than grade of amyloid deposits dictates size of the bleed. Presence of co-morbidities such as antiplatelet agents may predispose to haemorrhage.

Retinal metabolic and structural alterations in response to aflibercept treatment in neovascular age‐related macular degeneration

Non-invasive retinal markers of disease activity could pave the way for individualized treatment in neovascular age-related macular degeneration (nAMD). We aimed to evaluate if retinal vascular oxygen saturation and calibres could predict the initial treatment response after a loading phase of intravitreal aflibercept in nAMD. A total of 149 eyes were included (nAMD, n=76; dry AMD, n=30; normal eyes n=43). Of these, 57 treatment-naïve eyes with nAMD received three monthly injections with 2.0mg aflibercept and were subsequently stratified according to functional and structural response according to development in best-corrected visual acuity and macular retinal thickness. The retinal vascular oxygen saturation and calibres were measured prior to treatment and 1month after the third injection. Patients with nAMD and dry AMD had higher retinal arteriolar oxygen saturation as compared to normal eyes (94.3% versus 95.2% versus 92.6%, p=0.04). Thirty-nine (68.4%) and 12 (21.1%) eyes with nAMD were functional and structural responders. After the loading phase, structural nonresponders developed a higher retinal arteriolar (95.3% versus 93.3%, p=0.03) and venular (64.7% versus 59.4%, p=0.02) oxygen saturation, and responders developed a lower retinal arteriolar calibre (118.0 versus 114.3μm, p<0.01). In a multiple logistic regression model, increasing retinal venular oxygen saturation associated with a negative structural treatment outcome (odds ratio 1.17 for each 1% increment after the loading phase, 95% confidence interval 1.01-1.36, p=0.03). Changes in the retinal venular oxygen saturation associate independently with initial treatment response in nAMD, but functional and structural retinal measurements prior to treatment could not predict the treatment response.

Retinal Vasculature Reactivity During Flicker Light Provocation, Cardiac Stress and Stroke Risk in Africans: The SABPA Study.

Structural and functional similarities exist between the retinal, cerebral and, as previously suggested, the coronary microvasculature. Retinal microvascular structure and functionality (in response to flicker-light-induced-provocation (FLIP)) may relate to coronary artery disease risk and possible stroke risk. We investigated associations between retinal vessel structure, functionality and cardiac stress markers (cardiac troponin T [cTnT], amino-terminal B-type natriuretic peptide [NT-proBNP]) to translate these retina-heart relationships to stroke risk. We included 317 African and Caucasian teachers' (aged 23-68years), who participated in the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study. Fasting plasma and serum samples for cTnT and NT-proBNP were collected. Retinal vascular calibres were quantified from fundus images and dynamic retinal vessel calibre responses during FLIP. The University of California stroke risk score was applied to assess sub-clinical 10-year stroke risk. cTnT levels were similar in Africans and Caucasians, whereas NT-proBNP levels were lower in Africans. In Africans, a reduced arteriolar calibre and attenuated arteriolar dilation during FLIP was associated with higher cTnT (p < 0.01). Their larger retinal-venular calibre (p < 0.02) and attenuated arteriolar dilation during FLIP (p < 0.05) were associated with lower NT-proBNP. Again, exclusively in Africans, increased cardiac stress, wider venular calibres and retinal arteriovenous nicking predicted an increased 10-year stroke risk with odds ratios of 1.57 (95% CI, 1.34; 1.68, p = 0.031), 1.51 (95% CI, 1.26; 1.59, p = 0.002), 1.10 (95% CI, 0.94; 2.85, p = 0.002) and 1.06 (95% CI 0.83; 1.56, p = 0.052), respectively. None of these associations were evident in the Caucasian group. Investigating the retinal vasculature may serve as a tool to approximate sub-clinical coronary and cerebral microvasculature damage or dysfunction. These cardiac stress-retinal associations additionally predicted a greater stroke risk in the SABPA African cohort. Observable changes in the retinal vasculature may serve as markers for the identification and prediction of cardio-systemic and cerebral vascular morbidities and risks, thereby establishing a brain-heart link. Graphical Abstract Proposed series of events during which sustained high pressure and increased cardiac stress may alter retinal reactivity and link to increased stroke risk.

Retinal microvasculature changes in amyloid-negative subcortical vascular cognitive impairment compared to amyloid-positive Alzheimer's disease

Background and purposeTo investigate small vessel abnormalities in patients with cognitive impairment, we compared retinal microvascular alterations between patients with cognitive impairment related to Alzheimer's disease (ADCI) and those with subcortical vascular cognitive impairment (SVCI). MethodsWe prospectively recruited 29 amyloid-positive ADCI patients, 28 amyloid-negative SVCI patients that were confirmed by 11C-PiB-PET scan and 34 individuals with normal cognition (NC). The three groups were compared in terms of retinal vascular variables (retinal fractal dimension, vascular caliber, tortuosity and branching angle) by using a semi-automated, computer-assisted analysis of digital fundus photographs. We also investigated the relationship between retinal variables and white matter hyperintensities (WMH) on MRI. ResultsCompared to NC individuals, the SVCI patients had smaller total and arteriolar fractal dimensions, whereas there was no significant difference of fractal dimension between ADCI and NC. Other retinal variables did not differ among the three groups. A significant correlation existed between fractal dimension and WMH volume. ConclusionsRetinal microvascular alterations, especially retinal fractal dimension, may be useful markers that reflect cerebral microvascular changes in patients with SVCI as opposed to ADCI, who had no definite difference in retinal variables compared to the NC group.

Association of Meniere’s disease and retinal vascular calibre: a prospective observational study in China

ObjectiveIt is believed that Meniere’s disease (MD) is associated with vascular disorders, but few studies have reported the relationship between retinal vascular disorders and MD. We evaluated and compared the...

Changes in Retinal Vascular Caliber after Intravitreal Aflibercept Treatment for Diabetic Macular Oedema

Diabetic retinopathy is characterised by impaired retinal vascular autoregulation with signs of early retinal hyperperfusion and subsequent capillary drop out and peripheral ischemia. Initial retinal vascular dilation indicates disease progression and subsequent constriction signals a proliferative state. In this pilot study, we examined the effect of intravitreal aflibercept on retinal vessel diameter in patients with diabetic macular oedema. Twelve eyes of nine treatment-naive patients with diabetic macular oedema were examined during the first three months of treatment with aflibercept. The calibers of retinal arteries and veins and the central retinal arterial and vein equivalent were registered over the course of treatment. The evolution of the diabetic macular oedema was also registered and correlated to the retinal vascular caliber. During treatment, there was a significant reduction in the diameter of retinal arteries as well as in the central retinal arterial equivalent. The calibers of the retinal veins were also reduced, but not significantly. Macular oedema was significantly reduced, which however did not correlate with the vascular caliber changes. This pilot study demonstrates for the first time a possible significant reduction in retinal arterial caliber under aflibercept treatment for diabetic macular oedema. Further studies are needed to verify whether this response to intravitreal anti-VEGF treatment also signifies an improvement in retinal vascular homeostasis.